The Effect of High Salt Diet in the Regulation of Prolyl hydroxylase Domain‐containing Protein (PHD1) and associated genes in the mouse kidney

Abstract

Introduction PHD1 is an enzyme responsible for the degradation of Hypoxia inducible factor (HIF 1α) expressed in many tissues including the renal medulla. HIF 1α is a transcription factor that is expressed in tissues when exposed to hypoxic conditions. There is a reciprocal relationship between PHD1 and HIF 1α. Target genes of HIF 1α include heme oxygenase (HO1), and nitric oxide synthase (NOS2). High salt diet can cause hypoxia in renal medulla leading to changes in PHD1, HIF 1α, HO1, and NOS2 activity. Hypothesis High salt (HS) diet will cause a decrease in PHD1 activity and expression via changes in HO1 and NOS2 activity as an adaptive mechanism for the salt stimulus. Objecive To evaluate the effect of high salt diet on the regulation of PHD1, HIF 1α, HO1, and NOS2. To evaluate the modulation by hydralazine of PHD1 on HIF1 α, HO1, and NOS2 activity and expression (in the presence of a high or low salt diet). Materials & Methods Peroxisome proliferator-activated receptor (PPARα) mice-adult WT and KO of both sexes, were treated with the following: High salt diet (8% NaCl) with/without hydralazine (24mg/kg) in drinking water, and low salt diet (0.05% NaCl) with/without hydralazine in drinking water. Results Changes in water and sodium balance is not dependent on PPARα. Changes in water, and sodium balance caused by hydralazine is independent of PPARα expression. HO1 changes in expression and activity dependent on the PPARα. Changes in HO1, and NOS2 caused by hydralazine is also dependent on PPARα expression. Changes in PHD1 expression in the renal medulla were more pronounced than in the renal cortex. Conclusion Salt status defines the changes in PHD1, HIF 1α, NOS2, and HO1 and these changes take place in the renal medulla.